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Deconstructing the direct reciprocal hippocampal-anterior thalamic pathways for spatial learning

Nelson, Andrew J. D., Kinnavane, Lisa, Amin, Eman, O’Mara, Shane M. and Aggleton, John P. 2020. Deconstructing the direct reciprocal hippocampal-anterior thalamic pathways for spatial learning. Journal of Neuroscience 40 (36) , pp. 6978-6990. 10.1523/JNEUROSCI.0874-20.2020

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Abstract

The hippocampus is essential for normal memory but does not act in isolation. The anterior thalamic nuclei may represent one vital partner. Using DREADDs, the behavioral consequences of transiently disrupting anterior thalamic function was examined, followed by inactivation of the dorsal subiculum. Next, the anterograde transport of an adeno-associated virus expressing DREADDs was paired with localized intracerebral infusions of a ligand to target specific input pathways. In this way, the direct projections between the anterior thalamic nuclei and the dorsal hippocampal formation were inhibited, followed by separate inhibition of the dorsal subiculum projections to the anterior thalamic nuclei. To assay spatial working memory, all animals performed a reinforced T-maze alternation task, then a more challenging version that nullifies intra-maze cues. Across all four experiments, deficits emerged on the spatial alternation task that precluded the use of intra-maze cues. Inhibiting dorsal subiculum projections to the anterior thalamic nuclei produced the severest spatial working memory deficit. This deficit revealed the key contribution of dorsal subiculum projections to the anteromedial and anteroventral thalamic nuclei for the processing of allocentric information, projections not associated with head-direction information. The overall pattern of results provides consistent causal evidence of the two-way functional significance of direct hippocampal-anterior thalamic interactions for spatial processing. At the same time, these findings are consistent with hypotheses that these same, reciprocal interactions underlie the common core symptoms of temporal lobe and diencephalic anterograde amnesia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Publisher: Society for Neuroscience
ISSN: 1529-2401
Funders: Wellcome Trust
Date of First Compliant Deposit: 28 July 2020
Date of Acceptance: 19 July 2020
Last Modified: 07 Sep 2020 11:38
URI: http://orca.cf.ac.uk/id/eprint/133825

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